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Full-Text Articles in Life Sciences

Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo Aug 2020

Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo

Legacy Theses & Dissertations (2009 - 2024)

The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …


Investigation Of Phosphoserine Aminotransferase 1(Psat1) In Breast Cancer Progression., Stephanie Metcalf Dec 2019

Investigation Of Phosphoserine Aminotransferase 1(Psat1) In Breast Cancer Progression., Stephanie Metcalf

Electronic Theses and Dissertations

This dissertation describes my research into the involvement of phosphoserine aminotransferase 1 (PSAT1) in breast cancer progression; specifically, in triple negative breast cancer (TNBC) metastasis and endocrine resistance in estrogen receptor positive breast cancer (ER+BC). Breast cancer is the most common tumor diagnosis among women. While the overall 5-year survival for breast cancer is reaching 90%, the 5-year survival for metastatic disease is only 22%. Metastasis and endocrine resistance combined can affect over 50% of patients. One of the proteins and pathways implicated in both metastasis and endocrine resistance in breast cancer is phosphoserine aminotransferase 1 (PSAT1) and the serine …


Evaluating The Effects Of Vitamin D And Hyaluronic Acid On The Radiation Response Of Normal Mammary Epithelial Cells And Breast Cancer Cells, Lauren Rose-Boehnlein Jan 2018

Evaluating The Effects Of Vitamin D And Hyaluronic Acid On The Radiation Response Of Normal Mammary Epithelial Cells And Breast Cancer Cells, Lauren Rose-Boehnlein

Legacy Theses & Dissertations (2009 - 2024)

Each year over 200,000 American women are diagnosed with breast cancer. Nearly 25% of them are told they have triple negative breast cancer (TNBC), the most aggressive and lethal form, with few targeted treatment options beyond the standard regimen of surgery, chemotherapy, and radiotherapy. Over 40% of TNBC cases overexpress hyaluronan synthase 2 (HAS2), a cell membrane enzyme that synthesizes the extracellular matrix (ECM) polysaccharide hyaluronic acid (HA). HA binds to and activates the cell surface receptor CD44, which is highly enriched on the cell surface of cancer stem cells (CSCs) and has been associated with epithelial to mesenchymal transition …


Altered Lipid Metabolism And Adipocyte Activity Support Her2+ Breast Cancer Progression, Jason Wong Jan 2017

Altered Lipid Metabolism And Adipocyte Activity Support Her2+ Breast Cancer Progression, Jason Wong

Legacy Theses & Dissertations (2009 - 2024)

Overexpression of HER2 (ERBB2/neu) in breast cancer is an established clinical marker for aggressive disease and increased mortality. HER2+ breast cancers have increased protein levels of Human Epidermal Growth Factor Receptor 2 and overexpression of its coding gene, ERBB2. Many HER2+ tumors feature concomitant co-expression of the Nuclear Receptor subfamily 1, Group D, Member 1 (NR1D1/RevERBα) which regulates adipogenesis and circadian rhythm; the dysregulation of these two processes are known risk factors for breast cancer. HER2+ breast cancer cells have increased lipid synthesis, with evidence suggesting that NR1D1 is responsible for the upregulation of several genes in the de novo …


Restriction And Characterization Of Human Breast Cancer Using A Three-Dimensional Embryonic Stem Cell Model, Bridget Mooney Jan 2016

Restriction And Characterization Of Human Breast Cancer Using A Three-Dimensional Embryonic Stem Cell Model, Bridget Mooney

Legacy Theses & Dissertations (2009 - 2024)

Human breast cancer is currently the highest diagnosed form of cancer and the second leading cause of cancer-related deaths in American women. Triple negative breast cancer is of the basal subtype and displays the worst prognosis owing to its highly metastatic properties. Current treatments focused on eradicating breast tumors in lieu of or following local therapy include chemotherapy, hormonal therapy, and targeted therapy. Hormonal therapy is not an option for triple negative breast cancer as it does not contain hormone receptors and there are currently no approved biological targeted therapies. Chemotherapy has proven unsuccessful because triple negative breast cancer is …


Vitamin D Regulates Metabolic Gene Expression, Glutamate And Glutamine Utilization, And Mitochondrial Function In Human Mammary Epithelial Cells, Sarah Beaudin Jan 2015

Vitamin D Regulates Metabolic Gene Expression, Glutamate And Glutamine Utilization, And Mitochondrial Function In Human Mammary Epithelial Cells, Sarah Beaudin

Legacy Theses & Dissertations (2009 - 2024)

Exposure to 1,25-Dihydroxyvitamin D (1,25D) decreases proliferation and induces differentiation in telomerase-immortalized human mammary epithelial (hTERT-HME1) cells. The studies described here addressed the mechanisms by which these effects are exerted. Microarray experiments were used to identify a subset of metabolic genes and pathways that are altered by 1,25D. In particular, genes involved in glutamate and glutamine utilization, including SLC1A1 and GLUL, were studied. Interestingly, qPCR analysis in a panel of six cell lines, representing either normal epithelial tissue or breast cancer, demonstrated diverse gene expression responses to 1,25D. In an isogenic model of mammary cell transformation, 1,25D altered gene expression …


Molecular Actions Of The Novel Histone Deacetylase Inhibitor Cg-1521 In Models Of Inflammatory Breast Cancer, Namita Chatterjee Jan 2014

Molecular Actions Of The Novel Histone Deacetylase Inhibitor Cg-1521 In Models Of Inflammatory Breast Cancer, Namita Chatterjee

Legacy Theses & Dissertations (2009 - 2024)

Inflammatory breast cancer (IBC) is a rare and particularly lethal form of breast cancer. Despite aggressive therapeutic approaches, the 5-year survival rate is only 34%. As this disease is severely understudied, we have investigated the therapeutic potential of the novel hydroxamic acid-derived histone deacetylase inhibitor (HDACi), CG-1521 in comparison to a structurally similar compound, Trichostatin A (TSA) in two IBC cell lines: SUM149PT and SUM190PT. In these cells, CG-1521 and TSA induce dose- and time-dependent induction of cell cycle arrest and apoptosis regardless of the presence of 17β-estradiol (E2). Interestingly, the cell lines have considerably different sensitivities to these treatments …


Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta Jan 2014

Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta

Legacy Theses & Dissertations (2009 - 2024)

1,25-Dihydroxyvitamin D (1,25D) exerts anti-cancer actions through the vitamin D receptor (VDR) but the specific targets that mediate these effects remain to be defined. In these studies, growth and genomic responses to 1,25D were evaluated in a cellular model system derived from mammary tumors generated in VDR knockout (KO) and wildtype (WT) mice. WT145 cells (derived from WT tumors) expressed VDR and were growth inhibited by 1,25D, whereas KO240 cells (derived from VDRKO tumors) lacked VDR and were not growth inhibited by 1,25D. KO240 cell clones stably expressing VDR (KOhVDR cells) were sensitized to 1,25D mediated growth arrest. Genomic profiling …


Notch-1 Specifically Activates Erk1/2 In Multiple Breast Cancer Subtypes, Allison Schuyler Rogowski Jan 2011

Notch-1 Specifically Activates Erk1/2 In Multiple Breast Cancer Subtypes, Allison Schuyler Rogowski

Master's Theses

Notch-1 is a cell fate regulatory protein and a potent breast oncogene. Notch-1 and its ligand Jagged-1 are over-expressed in human breast cancers that are associated with poor overall survival (Reedijk, Odorcic et al. 2005). Deregulated Notch signaling may contribute to tumorigenesis by increasing proliferation, inhibiting differentiation, and preventing apoptosis (Miele, Golde et al. 2006). The mitogen-activated protein kinase (MAPK) pathway is a critical cell signaling pathway that has been implicated in the development and progression of cancer (Hanahan and Weinberg 2000). Four major MAPK pathways are involved in both cell growth and apoptosis. The regulation of these pathways is …


Regulation Of The Aryl Hydrocarbon Receptor And The Signal Transducer And Activator Of Transcription 1 By Long-Term Estrogen Exposure In Breast Carcinoma Cells, Neal Englert Jan 2011

Regulation Of The Aryl Hydrocarbon Receptor And The Signal Transducer And Activator Of Transcription 1 By Long-Term Estrogen Exposure In Breast Carcinoma Cells, Neal Englert

Legacy Theses & Dissertations (2009 - 2024)

The risk of developing breast cancer is known to be associated with a woman's lifetime exposure to estrogens, both endogenous and exogenous. Increased exposure to estrogens stimulates cellular proliferation, which is a widely accepted theory of estrogen receptor positive mammary carcinogenesis. The molecular mechanisms of gene expression regulation in response to long-term estrogen exposure (LTEE) of MCF-7 breast cancer cells were addressed in this study, with a focus on the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 1 (STAT1).


An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert Jan 2009

An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert

Legacy Theses & Dissertations (2009 - 2024)

The receptor protein tyrosine kinases (RPTKs) and the non- receptor protein tyrosine kinases (PTKs) are among the most commonly up-regulated genes found in all types of cancers. Although, a large body of data implicates a majority of tyrosine kinases (TKs) in cancer, few have been extensively evaluated for any potential therapeutic benefit in any of the many subtypes of breast cancer. We have used RNA interference (RNAi) to perform a large-scale loss-of-function analysis to facilitate the identification of individual factors necessary for the survival of an ErbB2 positive breast cancer cell line. We have found that 30% of the TKs …